Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development

被引:18
作者
Yang, Xianfa [1 ]
Hu, Boqiang [2 ]
Liao, Jiaoyang [1 ]
Qiao, Yunbo [3 ]
Chen, Yingying [1 ]
Qian, Yun [1 ]
Feng, Su [1 ]
Yu, Fang [1 ]
Dong, Ji [2 ]
Hou, Yu [2 ]
Xu, He [1 ]
Wang, Ran [1 ]
Peng, Guangdun [1 ,4 ,5 ,6 ,7 ]
Li, Jinsong [1 ,8 ]
Tang, Fuchou [2 ,9 ,10 ]
Jing, Naihe [1 ,7 ,8 ]
机构
[1] Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,Univ Chinese Acad Sci, Shanghai 200031, Peoples R China
[2] Peking Univ, Coll Life Sci, Beijing Adv Innovat Ctr Genom, Beijing 100871, Peoples R China
[3] Guangzhou Univ, Precise Genome Engn Ctr, Sch Life Sci, Guangzhou 510006, Guangdong, Peoples R China
[4] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China
[5] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China
[6] Guangzhou Regenerat Med & Hlth Guangdong Lab GRMH, Guangzhou 510005, Guangdong, Peoples R China
[7] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China
[8] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
[9] Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
[10] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
基金
中国国家自然科学基金;
关键词
STEM-CELLS; DEFINITIVE ENDODERM; DNA METHYLATION; CHROMATIN; DIFFERENTIATION; SPECIFICATION; LANDSCAPES; EXPRESSION; PLASTICITY; H3K27ME3;
D O I
10.1038/s41422-019-0234-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Primary germ layers have the potential to form all tissues in the mature organism, and their formation during gastrulation requires precise epigenetic modulation of both proximal and distal regulatory elements. Previous studies indicated that spatial and temporal patterns of gene expression in the gastrula predispose individual regions to distinct cell fates. However, the underlying epigenetic mechanisms remain largely unexplored. Here, we profile the spatiotemporal landscape of the epigenome and transcriptome of the mouse gastrula. We reveal the asynchronous dynamics of proximal chromatin states during germ layer formation as well as unique gastrula-specific epigenomic features of regulatory elements, which have strong usage turnover dynamics and clear germ layerspecific signatures. Importantly, we also find that enhancers around organogenetic genes, which are weakly expressed at the gastrulation stage, are frequently pre-marked by histone H3 lysine 27 acetylation (H3K27ac) in the gastrula. By using the transgenic mice and genome editing system, we demonstrate that a pre-marked enhancer, which is located in the intron of a brain-specific gene 2510009E07Rik, exhibits specific enhancer activity in the ectoderm and future brain tissue, and also executes important function during mouse neural differentiation. Taken together, our study provides the comprehensive epigenetic information for embryonic patterning during mouse gastrulation, demonstrates the importance of gastrula pre-marked enhancers in regulating the correct development of the mouse embryo, and thus broadens the current understanding of mammalian embryonic development and related diseases.
引用
收藏
页码:911 / 926
页数:16
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